Vortioxetine for Cognitive Impairment in Major Depressive Disorder During Post-COVID Syndrome: Real-World Evidence.

Objective: To compare the effectiveness of vortioxetine versus escitalopram and sertraline as a treatment in individuals with major depressive disorder (MDD) and post-COVID syndrome (PCS). Methods: This is a prospective, open-label, comparative effectiveness study in individuals with new-onset MDD as PCS outcome. The study was carried out in 1 clinical site. Individuals who had a history of confirmed SARS-CoV 2 infection, who met World Health Organization-defined criteria for PCS, and who met new-onset of MDD criteria according to DSM-5-TR were included. Participants that were eligible were assigned to receive vortioxetine at 10-20 mg/d, escitalopram 10-20 mg/d, or sertraline 50-200 mg/d over 8 weeks. The primary and secondary outcomes were changes from baseline to end point in Digital Symbol Substitution Test (DSST) and Montgomery-Asberg Depression Rating Scale (MADRS) or Patient Reported Outcome Measurement Information System Fatigue Short Form 7a (PROMIS 7a), respectively. Data were collected during January 2022 and December 2023. Results: 140 participants were assigned to received vortioxetine (n = 70), escitalopram (n = 36), or sertraline (n = 34). Participants assigned to vortioxetine exhibited significant changes in DSST scores from baseline to end point compared to escitalopram or sertraline (least squares [LS] mean differences, 8.25; 95% CI, 6.25-10.25; P < .001; LS mean differences, 8.00; 95% CI, 5.95-10.06; P < .001, respectively). Participants in the vortioxetine treatment group reported significantly greater changes in total MADRS scores from baseline to end point compared to escitalopram or sertraline (LS mean differences, -4.06; 95% CI, -4.92 to -3.20; P < .001; LS mean differences, -3.94; 95% CI, -4.83 to -3.06; P < .001, respectively). Conclusion: Vortioxetine has a significant procognitive effect. Antidepressant effects and improvement in fatigue symptoms (PROMIS 7a) also were observed.